Metabolic Regulation-Mediated Reversion of the Tumor Immunosuppressive Microenvironment for Potentiating Cooperative Metabolic Therapy and Immunotherapy.

Tumor cells exhibit heightened glucose (Glu) consumption and increased lactic acid (LA) production, resulting in the formation of an immunosuppressive tumor microenvironment (TME) that facilitates malignant proliferation and metastasis. In this study, we meticulously engineer an antitumor nanoplatform, denoted as ZLGCR, by incorporating glucose oxidase, LA oxidase, and CpG oligodeoxynucleotide into zeolitic imidazolate framework-8 that is camouflaged with a red blood cell membrane. Significantly, ZLGCR-mediated consumption of Glu and LA not only amplifies the effectiveness of metabolic therapy but also reverses the immunosuppressive TME, thereby enhancing the therapeutic outcomes of CpG-mediated antitumor immunotherapy. It is particularly important that the synergistic effect of metabolic therapy and immunotherapy is further augmented when combined with immune checkpoint blockade therapy. Consequently, this engineered antitumor nanoplatform will achieve a cooperative tumor-suppressive outcome through the modulation of metabolism and immune responses within the TME.

Femtosecond Laser Fabrication of Three-Dimensional Bubble-Propelled Microrotors for Multicomponent Mechanical Transmission.

Inspired by the reverse thrust generated by fuel injection, micromachines that are self-propelled by bubble ejection are developed, such as microrods, microtubes, and microspheres. However, controlling bubble ejection sites to build micromachines with programmable actuation and further enabling mechanical transmission remain challenging. Here, bubble-propelled mechanical microsystems are constructed by proposing a multimaterial femtosecond laser processing method, consisting of direct laser writing and selective laser metal reduction. The polymer frame of the microsystems is first printed, followed by the deposition of catalytic platinum into the desired local site of the microsystems by laser reduction. With this method, a variety of designable microrotors with selective bubble ejection sites are realized, which enable excellent mechanical transmission systems composed of single and multiple mechanical components, including a coupler, a crank slider, and a crank rocker system. We believe the presented bubble-propelled mechanical microsystems could be extended to applications in microrobotics, microfluidics, and microsensors.

Effects of water fluoridation on early embryonic development of zebrafish.

Fluoride has strong electronegativity and exposes diversely in nature. Water fluoridation is the most pervasive form of occurrence, representing a significant threat to human health. In this study, we investigate the morphometric and physiological alterations triggered by fluoride stimulation during the embryogenesis of zebrafish and reveal its putative effects of stage- and/or dose-dependent. Fluoride exhibits potent biological activity and can be extensively absorbed by the yolk sac, exerting significant effects on the development of multiple organs. This is primarily manifested as restricted nutrient utilization and elevated levels of lipid peroxidation, further leading to the accumulation of superoxide in the yolk sac, liver, and intestines. Moreover, pericardial edema exerts pressure on the brain and eye development, resulting in spinal curvature and reduced body length. Besides, acute fluoride exposure with varying concentrations has led to diverse teratogenic outcomes. A low dose of water fluoridation tends to induce abnormal development of the embryonic yolk sac, while vascular malformation is widely observed in all fluoride-treated groups. The effect of fluoride exposure on blood circulation is universally present, even in zebrafish larvae that do not exhibit obvious deformities. Their swimming behavior is also affected by water fluoridation, resulting in reduced activity and delayed reactions. In conclusion, this study provides valuable insights into the monitoring of environmental quality related to water fluoridation and disease prevention.

Research on the dentification of Panax ginseng and Panax quinquefolium using catalysed hairpin assembly technology.

INTRODUCTION: Panax ginseng and Panax quinquefolium are traditional Chinese herb medicines and similar in morphology and some chemical components but differ in drug properties, so they cannot be mixed. However, the processed products of them are often sold in the form of slices, powder, and capsules, which are difficult to identify by traditional morphological methods. Furthermore, an accurate evaluation of P. ginseng, P. quinquefolium and the processed products have not been conducted. OBJECTIVE: This study aimed to establish a catalysed hairpin assembly (CHA) identification method for authenticating products made from P. ginseng and P. quinquefolium based on single nucleotide polymorphism (SNP) differences. METHOD: By analysing the differences of SNP in internal transcribed spacer 2 (ITS2) in P. ginseng and P. quinquefolium to design CHA-specific hairpins. Establish a sensitive and efficient CHA method that can identify P. ginseng and P. quinquefolium, use the sequencing technology to verify the accuracy of this method in identifying Panax products, and compare this method with high-resolution melting (HRM). RESULTS: The reaction conditions of CHA were as follows: the ratio of forward and reverse primers, 20:1; hairpin concentration, 5 ng/µL. Compared with capillary electrophoresis, this method had good specificity and the limit of detection was 0.5 ng/µL. The result of Panax product identification with CHA method were coincidence with that of the sequencing method; the positive rate of CHA reaction was 100%. CONCLUSION: This research presents an effective identification method for authenticating P. ginseng and P. quinquefolium products, which is helpful to improve the quality of Panax products.

4D Direct Laser Writing of Submerged Structural Colors at the Microscale.

Biomimetic stimuli-responsive structure colors (SCs) can improve the visualization and identification in the micro functional structure field such as information encryption/decryption and smart actuators. However, it is still challenging to develop the ability to 4D print arbitrary submerged colorful patterns with stimuli-responsive materials at the microscale. Herein, a hydrogel photoresist with feature resolution (98 nm) for the fabrication of 4D microscopic SCs by the femtosecond direct laser writing method is developed. The 4D printed woodpile SCs are grouped as pixel palettes with various laser parameters and they spanned almost the entire color space. The coloring mechanism of diffraction gratings is not only investigated by optics microscopy and spectroscopy but also supported by simulation. Moreover, the 4D printed hydrogel-integrated amphichromatic fish constructions and pixelated painting can visually discolor reversibly by regulating the solution pH. This finding promises an ideal coloring method for sensors, anti-counterfeiting labels, and transformable photonic devices.

Factors associated with delayed reporting for surgical care among patients with surgical acute abdomen attended at Muhimbili National Hospital: Tanzania.

BACKGROUND: Surgical acute abdomen is a sudden onset of severe abdominal symptoms (pain, vomiting, constipation etc.) indicative of a possible life-threatening intra-abdominal pathology, with most cases requiring immediate surgical intervention. Most studies from developing countries have focused on complications related to delayed diagnosis of specific abdominal problems like intestinal obstruction or acute appendicitis and only a few studies have assessed factors related to the delay in patients with acute abdomen. This study focused on the time from the onset of a surgical acute abdomen to presentation to determine factors that led to delayed reporting among these patients at the Muhimbili National Hospital (MNH) and aimed to close the knowledge gap on the incidence, presentation, etiology, and death rates for acute abdomen in Tanzania. METHODS: We conducted a descriptive cross-sectional study at MNH, Tanzania. Patients with a clinical diagnosis of the surgical acute abdomen were consecutively enrolled in the study over a period of 6 months and data on the onset of symptoms, time of presentation to the hospital, and events during the illness were collected. RESULTS: Age was significantly associated with delayed hospital presentation, with older groups presenting later than younger ones. Informal education and being uneducated were factors contributing to delayed presentation, while educated groups presented early, albeit the difference was statistically insignificant (p = 0.121). Patients working in the government sector had the lowest percentage of delayed presentation compared to those in the private sector and self-employed individuals, however, the difference was statistically insignificant. Family and cohabiting individuals showed late presentation (p = 0.03). Deficiencies in health care staff on duty, unfamiliarity with the medical facilities, and low experience in dealing with emergency cases were associated with the factors for delayed surgical care among patients. Delays in the presentation to the hospital increased mortality and morbidity, especially among patients who needed emergency surgical care. CONCLUSION: Delayed reporting for surgical care among patients with surgical acute abdomen in underdeveloped countries like Tanzania is often not due to a single reason. The causes are distributed across several levels including the patient's age and family, deficiency in medical staff on duty and lack of experience in dealing with emergency cases, educational level, working sectors, socioeconomic and sociocultural status of the country.

Screening Key Pathogenic Genes and Small Molecule Compounds for PNET.

Primitive neuroectodermal tumors (PNET) are rare malignant tumors, but the mortality rate of the patients is extremely high. The aim of this study was to identify the hub genes and pathways involved in the pathogenesis of PNET and to screen the potential small molecule drugs for PNET. We extracted gene expression profiles from the Gene Expression Omnibus database and identified differentially expressed genes (DEGs) through Limma package in R. Two expression profiles (GSE14295 and GSE74195) were downloaded, including 33 and 5 cases separately. Four hundred sixty-eight DEGs (161 upregulated; 307 downregulated) were identified. Functional annotation and KEGG pathway enrichment of the DEGs were performed using DAVID and Kobas. Gene Ontology analysis showed the significantly enriched Gene Ontology terms included but not limited to mitosis, nuclear division, cytoskeleton, synaptic vesicle, syntaxin binding, and GABA A receptor activity. Cancer-related signaling pathways, such as DNA replication, cell cycle, and synaptic vesicle cycle, were found to be associated with these genes. Subsequently, the STRING database and Cytoscape were utilized to construct a protein-protein interaction and screen the hub genes, and we identified 5 hub genes (including CCNB1, CDC20, KIF11, KIF2C, and MAD2L1) as the key biomarkers for PNET. Finally, we identified potential small molecule drugs through CMap. Seven small molecule compounds, including trichostatin A, luteolin, repaglinide, clomipramine, lorglumide, vorinostat, and resveratrol may become potential candidates for PNET drugs.

A novel aptamer beacon for rapid screening of recombinant cells and in vivo monitoring of recombinant proteins.

Recombinant protein drugs, which are typically produced by mammalian host cells, have been approved for the treatment of a range of diseases. Accordingly, systems for selecting recombinant cell lines with efficient protein expression and for testing the content of recombinant proteins in vivo are crucial to the large-scale production and application of protein-based therapeutic drugs. In this study, we designed three aptamer beacons to detect His-tag, a common label of recombinant proteins. We found that all three beacons could specifically and quantitatively measure the His-tagged recombinant proteins with a short reaction time. Among these three beacons, the 6H5-MU beacon had the highest sensitivity for His polypeptides with a detection limit of 250 ng/mL and the shortest detection time within 1 min. Furthermore, we established a rapid and highly effective recombinant cell line construction system, which could obtain monoclonal cell lines with high yields of target proteins within 21 days, by combining 6H5-MU with pSB, a novel plasmid composed of a Sleeping Beauty transposase and a transposon. Finally, 6H5-MU also discriminately tested the serum concentration of His-tagged recombinant proteins in vivo, with consistent results compared to enzyme-linked immunosorbent assay (ELISA). We thus established a rapid and high-throughput method for generating recombinant cell lines and in vivo monitoring of recombinant protein levels, thereby providing a new platform for the development and preparation of recombinant protein drugs. KEY POINTS: • The 6H5-MU aptamer beacon rapidly and accurately binds to His-tagged recombinant proteins. • A system for rapid and high-throughput generation of recombinant cell lines is established using 6H5-MU and pSB. • 6H5-MU allows in vivo monitoring of recombinant protein levels.

Gonioscopy-assisted transluminal trabeculotomy for open-angle glaucoma with failed incisional glaucoma surgery: two-year results.

BACKGROUND: To evaluate the safety and efficacy of gonioscopy-assisted transluminal trabeculotomy (GATT) in treating patients with open-angle glaucoma (OAG) who had failed prior incisional glaucoma surgery. METHODS: A consecutive case series of OAG patients aged ≥ 18 who underwent GATT with previous failed glaucoma incision surgery was retrospectively analyzed. Main outcome measures included intraocular pressure (IOP), the number of glaucoma medications, surgical success rate, and occurrence of complications. Success was defined as an IOP of ≤ 21 mmHg and a reduction of IOP by 20% or more from baseline with (qualified success) or without (complete success) glaucoma medications. For eyes with preoperative IOP of < 21 mmHg on 3 or 4 glaucoma medications, postoperative IOP of ≤ 18 mmHg without any glaucoma medications was also defined as complete success. RESULTS: Forty-four eyes of 35 patients (21 with juvenile-onset open-angle glaucoma and 14 with adult-onset primary open-angle glaucoma) with a median age of 38 years were included in this study. The proportion of eyes with 1 prior incisional glaucoma surgery was 79.5%, and the others had 2 prior surgeries. IOP decreased from 27.4 ± 8.8 mm Hg on 3.6 ± 0.7 medications preoperatively to 15.3 ± 2.7 mm Hg on 0.5 ± 0.9 medications at the 24-month visit (P < 0.001). The mean IOP and the number of glaucoma medications at each follow-up visit were lower than the baseline (all P < 0.001). At 24 months postoperatively, 82.1% of the eyes had IOP ≤ 18 mmHg (versus 15.9% preoperatively, P < 0.001), 56.4% reached IOP ≤ 15 mmHg (versus 4.6% preoperatively, P < 0.001), and 15.4% achieved IOP ≤ 12 mmHg (compared to none preoperatively, P = 0.009). While 95.5% of eyes took 3 or more medications preoperatively, 66.7% did not take glaucoma medication 24 months after GATT. Thirty-four (77.3%) eyes achieved IOP reduction greater than 20% on fewer medications. The complete and qualified success rates were 60.9% and 84.1%, respectively. No vision-threatening complications occurred. CONCLUSIONS: GATT was safe and effective in treating refractory OAG patients who failed prior incisional glaucoma surgery.

Functional Shape-Morphing Microarchitectures Fabricated by Dynamic Holographically Shifted Femtosecond Multifoci.

Functional microdevices based on responsive hydrogel show great promise in targeted delivery and biomedical analysis. Among state-of-the-art techniques for manufacturing hydrogel-based microarchitectures, femtosecond laser two-photon polymerization distinguishes itself by high designability and precision, but the point-by-point writing scheme requires mechanical apparatuses to support focus scanning. In this work, by predesigning holograms combined with lens phase modulation, multiple femtosecond laser spots are holographically generated and shifted for prototyping of three-dimensional shape-morphing structures without any moving equipment in the construction process. The microcage array is rapidly fabricated for high-performance target capturing enabled by switching environmental pH. Moreover, the built scaffolds can serve as arrayed analytical platforms for observing cell behaviors in normal or changeable living spaces or revealing the anticancer effects of loaded drugs. The proposed approach opens a new path for facile and flexible manufacturing of hydrogel-based functional microstructures with great versatility in micro-object manipulation.

Medium-Term Prognostic Implications of Cardiac Magnetic Resonance Imaging in Patients With Myocardial Infarction With Nonobstructive Coronary Arteries (MINOCA): A Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to evaluate the medium-term prognostic implications of cardiac magnetic resonance (CMR) imaging in patients with myocardial infarction with non-obstructive coronary arteries (MINOCA). METHODS: A systematic literature search of Embase, PubMed, and The Cochrane Library was performed. Eligible studies reported outcomes of CMR-assessed MINOCA with a mean follow-up period of >6 months. The primary endpoint was all-cause death. Secondary endpoints included cardiac death, reinfarction, and cardiovascular rehospitalisation. The pooled effect sizes with 95% confidence interval (CIs) were estimated using a random effect model. RESULTS: A total of 3,050 patients from twenty-one studies were included in the meta-analysis. The prevalence of myocarditis, "true" myocardial infarction, Takotsubo cardiomyopathy, and normal CMR imaging was 36%, 25%, 14%, and 19%, respectively. Pooled data showed that the annualised event rates for all-cause mortality, cardiac mortality, reinfarction, and cardiovascular rehospitalisation were 1.01% (95% CI 0.59%-1.51%), 0.06% (95% CI 0.00%-0.39%), 0.68% (95% CI 0.18%-1.38%), and 5.67% (95% CI 3.11%-8.85%), respectively. Compared with patients with a diagnosis of myocarditis on CMR, patients with Takotsubo cardiomyopathy (RR 7.11; 95% CI 3.04-16.66) and "true" myocardial infarction (RR 3.82; 95% CI 1.65-8.86) were associated with a significantly higher risk of all-cause mortality, whereas a similar risk of all-cause mortality was observed in patients with normal imaging (RR 1.01; 95% CI 0.28-3.59). No association was found between CMR diagnoses and the risk of secondary endpoints in MINOCA. CONCLUSIONS: In patients with MINOCA assessed by CMR, the overall absolute incidence rates of mortality and reinfarction were low. However, certain imaging diagnoses were associated with a higher risk of all-cause mortality, with most deaths attributed to non-cardiac causes. Additionally, these patients experienced a high burden of cardiovascular rehospitalisation. REGISTRATION: PROSPERO (CRD42022323615).

Leisure crafting and work engagement among Chinese ICU nurses: The multiple mediation effect of recovery experience and humanistic care ability.

AIMS: Based on the conservation of resources theory, this study explored the intermediary role of intensive care unit (ICU) nurses' recovery experience and humanistic care ability between leisure crafting and work engagement. BACKGROUND: As the ICU is an important life-saving department, the level of work engagement of nurses directly affect the quality of life and health outcomes of patients. Actively seeking countermeasures to improve the work engagement level of ICU nurses is of great significance to enhancing the nursing quality of the ICU. According to the theory of resource conservation, the resources owned by individuals are limited and must be replenished promptly and effectively to maintain relatively stable physical, mental, and working states. Therefore, determining ways for ICU nurses to supplement the consumed resources effectively and efficiently in a limited time to maintain a high level of work engagement is the main concern of this study. METHODS: In this cross-sectional study from January 2023 to March 2023, 478 ICU nurses were recruited by convenience sampling. The survey tools included the Leisure Crafting Scale, the Utrecht Work Engagement Scale-9, the Caring Ability Inventory, and the Recovery Experience Questionnaire. Descriptive data and Pearson correlation coefficients were analyzed via SPSS 26.0 (IBM Corp.). PROCESS v4.0 (by Andrew F. Hayes) Macro Model 6 was applied to analyze the serial multiple mediator models. We used the STROBE checklist to report the results. RESULTS: First, the results showed that leisure crafting, humanistic care ability, and recovery experience were positively correlated with work engagement. Second, recovery experience and humanistic care ability played a partially mediating role between leisure crafting and work engagement, respectively. Third, recovery experience and humanistic care ability also had a serial mediation effect between leisure crafting and work engagement. CONCLUSION: The findings of the study indicated that improving nurses' active control of leisure time may have particularly positive effects on ICU nurses' work engagement through increasing recovery experience and humanistic care ability. IMPLICATIONS FOR NURSING AND NURSING POLICY: Administrators can formulate intervention measures to improve the leisure crafting level of ICU nurses, promote work-life balance, which enhances recovery and supports engagement with patient-focused humanistic care, and have a positive impact on the work engagement of ICU nurses.

Rapid and Multimaterial 4D Printing of Shape-Morphing Micromachines for Narrow Micronetworks Traversing.

Micromachines with high environmental adaptability have the potential to deliver targeted drugs in complex biological networks, such as digestive, neural, and vascular networks. However, the low processing efficiency and single processing material of current 4D printing methods often limit the development and application of shape-morphing micromachines (SMMs). Here, two 4D printing strategies are proposed to fabricate SMMs with pH-responsive hydrogels for complex micro-networks traversing. On the one hand, the 3D vortex light single exposure technique can rapidly fabricate a tubular SMM with controllable size and geometry within 0.1 s. On the other hand, the asymmetric multimaterial direct laser writing (DLW) method is used to fabricate SMMs with designable 3D structures composed of hydrogel and platinum nanoparticles (Pt NPs). Based on the presence of ferroferric oxide (Fe3 O4 ) and Pt NPs in the SMMs, efficient magnetic, bubble, and hybrid propulsion modes are achieved. Finally, it is demonstrated that the spatial shape conversion capabilities of these SMMs can be used for narrow micronetworks traversing, which will find potential applications in targeted cargo delivery in microcapillaries.

Prelithiation Reagents and Strategies on High Energy Lithium-Ion Batteries.

Lithium-ion batteries (LIBs) have been widely employed in energy-storage applications owing to the relatively higher energy density and longer cycling life. However, they still need further improvement especially on the energy density to satisfy the increasing demands on the market. In this respect, the irreversible capacity loss (ICL) in the initial cycle is a critical challenge due to the lithium loss during the formation of solid electrolyte interphase (SEI) layer on the anode surface. The strategy of prelithiation was then proposed to compensate for the ICL in the anode and recover the energy density. Here, various methods of the prelithiation are summarized and classified according to the basic working mechanism. Further, considering the critical importance and promising progress of prelithiation in both fundamental research and real applications, this Review article is intended to discuss the considerations involved in the selection of prelithiation reagents/strategies and the electrochemical performance in full-cells. Moreover, insights are provided regarding the practical application prospects and the challenges that still need to be addressed.

Curcumin Improves Human Umbilical Cord-Derived Mesenchymal Stem Cell Survival via ERK1/2 Signaling and Promotes Motor Outcomes After Spinal Cord Injury.

Human umbilical cord-derived mesenchymal stem cell (hUC-MSC) transplantation is thought to be a promising strategy for treating spinal cord injury (SCI). However, the low survival rate of transplanted hUC-MSCs limits their clinical application in cell replacement therapy. Curcumin can suppress inflammation after SCI; however, it remains unknown whether curcumin can modulate the survival of transplanted hUC-MSCs. In this study, to investigate whether curcumin could strengthen the therapeutic effects of hUC-MSC transplantation on SCI, we induced hUC-MSC apoptosis with TNF-α, transplanted hUC-MSC into SCI rats, and assessed the antiapoptotic effect and mechanism of curcumin. LDH release analysis and flow cytometry demonstrated that TNF-α led to hUC-MSC apoptosis and that curcumin increased the hUC-MSC survival rate in a dose-dependent manner. In addition, we showed that the phosphorylation levels of ERK1/2, JNK, and P38 were upregulated in apoptotic hUC-MSCs, while curcumin increased the phosphorylation of ERK1/2 but did not activate JNK or P38, and these effects were reversed by the p42/44 antagonist U0126. Furthermore, we found that the motor function scores and number of surviving HNA-positive cells were significantly increased after curcumin and hUC-MSC transplantation therapy 8 weeks post-SCI, while U0126 markedly attenuated these effects. These data confirmed that curcumin suppressed hUC-MSC apoptosis through the ERK1/2 signaling pathway and that combined curcumin and hUC-MSC treatment improved motor function in rats after SCI. The current research provides a strong basis for hUC-MSC replacement therapy in conjunction with curcumin in the treatment and management of SCI in humans.

Critical window for the association between prenatal environmental tobacco smoke exposure and preterm birth.

Although environmental tobacco smoke (ETS) exposure is considered to be a severe public health problem and a modifiable risk factor for preterm birth (PTB), we still lack a comprehensive understanding of the PTB risk associated with trimester-specific prenatal ETS exposure. This study aimed to examine the accumulation of risk across trimester ETS exposure and the critical window of the association between maternal ETS exposure during pregnancy and PTB. A total of 63,038 mother-child pairs were involved in the analysis of the 2017 survey of Longhua Child Cohort Study. Information about socio-demographic characteristics, prenatal ETS exposure, and birth outcomes were collected using a self-report questionnaire. A series of logistic regression models were employed to assess the associations between prenatal ETS exposure and PTB. We found that maternal ETS exposure during pregnancy significantly increased the risk of PTB and this association increased with both the average level of daily ETS exposure and the number of trimesters of ETS exposure. Moreover, mothers who were initially exposed to ETS in the 1st trimester of pregnancy had significant higher risk of PTB (OR = 1.34, 95% CI: 1.25-1.44). Furthermore, mothers exposed to ETS in the 1st trimester only (OR = 1.26, 95%CI: 1.04-1.50), in both 1st and 2nd trimester (OR = 1.35, 95%CI: 1.08-1.67) and throughout pregnancy (OR = 1.35, 95%CI: 1.24-1.46) experienced a significantly high risk of PTB. Prenatal maternal ETS exposure during only the 2nd trimester also resulted in a high risk of PTB with marginal significance (OR = 1.33, 95% CI:0.78-2.13). To conclude, the 1st and early 2nd trimester might be the critical window for prenatal ETS exposure causing PTB.

Antifungal and Antibiofilm In Vitro Activities of Ursolic Acid on Cryptococcus neoformans.

Ursolic acid (UA) exists in a variety of medicinal plants. UA exhibits antimicrobial activity against several microorganisms; however, little is known regarding the potential antifungal effect of UA on Cryptococcus neoformans (C. neoformans). The antifungal and antibiofilm activities of UA on C. neoformans H99 were evaluated in this study. Minimum inhibitory concentration (MIC) of UA against C. neoformans H99 was determined by microdilution technique, and its action mode was elucidated by clarifying the variations in cell membrane integrity, capsule, and melanin production. Moreover, the inhibition and dispersal effects of UA on biofilm formation and mature biofilms by C. neoformans H99 were evaluated using crystal violet (CV) assay, optical microscopy, field emission scanning electron microscopy and confocal laser scanning microscopy. The results indicated that the MIC value of UA against C. neoformans H99 was 0.25 mg/mL. UA disrupted the cell membrane integrity, inhibited the capsule and melanin production of C. neoformans H99 in a concentration-dependent manner. Further, UA presented the inhibitory effect on biofilm formation and dispersed mature biofilms, as well as compromised the cell membrane integrity of C. neoformans H99 cells within biofilms. Together, these results indicate that UA might be a potential therapeutic option for the treatment of C. neoformans-related infections.

Framework of humanistic care for patients in the ICU: A preliminary study.

BACKGROUND: Humanistic care involves caring, concern, paying attention to people's individuality, meeting their needs and respecting their rights, which is the core concept and central task of nursing. Effective care can enhance patients' ability to deal with stress and promote patient recovery. Implementing humanistic care in the intensive care unit (ICU) is particularly important for health care providers. AIMS AND OBJECTIVES: This study aims to develop a framework of the humanistic care in the ICU. DESIGN: The qualitative research followed Strauss' procedural grounded theory approach. METHODS: Purposive sampling and theoretical sampling were used to select 12 nurses in the Department of Critical Medicine, 16 patients, and eight family members for semi-structured interviews from October 2020 to April 2021. Results were summarized and analysed through three-level coding based on grounded principles. RESULTS: Sixteen subcategories and six main categories were extracted after three-level coding, and the final ICU humanistic care framework was formed with home, activity, visit, environment, nursing and safety ("HAVENS") as the core. CONCLUSION: This study provides an explanatory theory of humanistic care in the ICU that can guide nurses' practice in ICU clinical work. RELEVANCE TO CLINICAL PRACTICE: This theory provides guidance for nurses to implement humanistic care in critical care practice to improve the ICU stay experience of critically ill patients.

Study of cellular heterogeneity and differential dynamics of autophagy in human embryonic kidney development by single-cell RNA sequencing.

BACKGROUND: Autophagy is believed to participate in embryonic development, but whether the expression of autophagy-associated genes undergoes changes during the development of human embryonic kidneys remains unknown. METHODS: In this work, we identified 36,151 human renal cells from embryonic kidneys of 9-18 gestational weeks in 16 major clusters by single-cell RNA sequencing (scRNA-seq), and detected 1350 autophagy-related genes in all fetal renal cells. The abundance of each cell cluster in Wilms tumor samples from scRNA-seq and GDC TARGET WT datasets was detected by CIBERSORTx. R package Monocle 3 was used to determine differentiation trajectories. Cyclone tool of R package scran was applied to calculate the cell cycle scores. R package SCENIC was used to investigate the transcriptional regulons. The FindMarkers tool from Seurat was used to calculate DEGs. GSVA was used to perform gene set enrichment analyses. CellphoneDB was utilized to analyze intercellular communication. RESULTS: It was found that cells in the 13th gestational week showed the lowest transcriptional level in each cluster in all stages. Nephron progenitors could be divided into four subgroups with diverse levels of autophagy corresponding to different SIX2 expressions. SSBpod (podocyte precursors) could differentiate into four types of podocytes (Pod), and autophagy-related regulation was involved in this process. Pseudotime analysis showed that interstitial progenitor cells (IPCs) potentially possessed two primitive directions of differentiation to interstitial cells with different expressions of autophagy. It was found that NPCs, pretubular aggregates and interstitial cell clusters had high abundance in Wilms tumor as compared with para-tumor samples with active intercellular communication. CONCLUSIONS: All these findings suggest that autophagy may be involved in the development and cellular heterogeneity of early human fetal kidneys. In addition, part of Wilms tumor cancer cells possess the characteristics of some fetal renal cell clusters.

Magnetic resonance-guided thermal ablation for small liver malignant tumor located on segment II or IVa abutting the heart: a retrospective cohort study.

OBJECTIVE: This study aimed to evaluate the clinical safety and efficacy magnetic resonance (MR)-guided percutaneous thermal ablation for the treatment of small liver malignant tumors of segment II and IVa (≤3.0 cm) abutting the heart. METHOD: The enrollment of 24 patients with 25 malignant liver lesions located on the II or IVa segment abutting the heart who underwent MRI-guided thermal ablation between August 2010 and February 2020 were retrospectively analyzed. Follow-up MRI was performed to evaluate the curative effect. Local tumor progression-free survival and overall survival rates were also calculated. RESULTS: The procedures including radiofrequency ablation (RFA) for 15 patients and microwave ablation (MWA) for 9 patients were successfully accomplished (technical success rate of 100%) without major complications. The mean duration time was 78.4 ± 29.4 min (40-140 min), and mean follow-up time was 31.5 ± 22.2 months (6-92 months). The technical efficacy was 100% following one ablation session with MRI assessment after one month. Local tumor progression was observed in one patient with a metastatic lesion located in segment II at 18 months follow-up. The progression-free survival time was 20.1 ± 16.9 months (median: 15 months). The 1-, 3-, and 5-year local tumor progression-free survival rates of this patient were 100%, 94.7%, and 94.7%, respectively. With regards to all the patients, the 1-, 3-, and 5-year estimated overall survival rates were 91.7%, 80.6%, and 50.1%, respectively. CONCLUSION: MR-guided thermal ablation is safe and effective for the treatment of small liver malignant tumors located on the II or IVa segment abutting the heart.